Abstract
Real-time monitoring of cancer cells’ phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as “cell signature”), without the need for isolating individual CTCs. We observe cell heterogeneity and phenotypic changes of melanoma cell lines during molecular targeted treatment. Furthermore, we follow the CTC signature changes of 10 stage-IV melanoma patients receiving immunological or molecular targeted therapies. Our technique maps the phenotypic evolution of patient CTCs sensitively and rapidly, and shows drug-resistant clones having different CTC signatures of potential clinical value. We believe our proposed method is of general interest in the CTC relevant research and translation fields.
Highlights
Real-time monitoring of cancer cells’ phenotypic evolution during therapy can provide vital tumour biology information for treatment management
We select four melanoma Circulating tumour cell (CTC) surface markers, including melanoma-chondroitin sulphate proteoglycan (MCSP) 17–22 and melanoma cell adhesion molecule (MCAM)[23,24,25,26] which are expressed in over 85 and 70% of the primary and metastatic melanoma lesions, respectively;[27, 28] erythroblastic leukaemia viral oncogene homologue 3 (ErbB3)[29], which is involved in therapy resistance development through activation of an alternative phosphoinositide 3-kinase–v-akt murine thymoma viral oncogene homologue (PI3K–AKT) pathway;[30, 31] and low-affinity nerve growth factor receptor (LNGFR)[32], a stem-cell biomarker which is strongly associated with resistance development[33]
Circulating tumour DNA is a complementary marker to CTCs for detecting recurring disease and monitoring disease progression or therapeutic success;[4, 8] it cannot be used for phenotypic classification
Summary
Real-time monitoring of cancer cells’ phenotypic evolution during therapy can provide vital tumour biology information for treatment management. We demonstrate the use of antibodyconjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as “cell signature”), without the need for isolating individual CTCs. We observe cell heterogeneity and phenotypic changes of melanoma cell lines during molecular targeted treatment. The CellSearch system, which is the only Food and Drug Administration (FDA)approved CTC detection technology, is an example of such technique[4] These strategies are prone to disregard tumour cells from (i) cancers of non-epithelial origin like melanoma, and (ii) cancers with downregulated EpCAM expression. Flow cytometry is one of the most commonly used techniques for cell characterisation but typically requires a relatively large quantity of sample cells and has limited multiplexing capabilities New technologies such as CyTOF may be able to overcome these limitations;[9] it does not allow for the collection of live cells for further analysis or imaging afterwards. We find that drug-resistant clones have different CTC phenotypes of potential clinical value
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
